Pathophysiology: T2DM

Pathophysiology
  • Type 2 is more complex than T1DM, with multiple mechanisms at work
    1. Insulin resistance  – Impaired sensitivity to insulin in the muscle, fat, and liver
      • This is the main factor in T2DM
      • The cause of this is unclear but is associated with adiposity, inactivity, and NAFLD
    2. Progressive B cell failure also causes reduced insulin release
      • Therefore they can still benefit from insulin therapy
      • This progresses with time
        • Not autoimmune (unlike type 1)
        • 20% of patients ultimately progress to no insulin release at all
      • a-cells remain normal and this further contributes to hyperglycaemia via glucagon release which is actually increased(to provide more glucose to the body’s cells by increasing the extracellular glucose)
Metabolic changes in T2DM
  • Like T1DM, metabolic disturbances again occur due to abnormal insulin

In most patients with T2DM, only the pro-anabolic effect of insulin is lost

  • This is because insulin resistance is the main factor
  • Even a small amount of insulin – as in T2DM – can prevent gluconeogenesis
  • Only patients who lose all ability to make insulin lose this (about 20% of patients with late-stage T2DM)
  1. Hyperglycaemia is the main issue – the features are identical to T1DM
    • Increased infection risk
    • Glycosuria => osmotic diuresis symptoms
Natural history of T2DM
  • With progression, several changes develop:
    1. Insulin secretion becomes impaired (eventually completely ceasing)
    2. Resistance plateaus quickly
    3. Glucose becomes progressively more poorly controlled because of the above reasons